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Séminaire impromptu - Yasunori HayashiRoles of cytoskeleton in hippocampal synaptic plasticity

Abstract :

Synaptic plasticity occurs as a result of biochemical reactions and protein interactions that take place within small volume of less than 1 fl. Application of traditional biochemical approaches is simply impractical to elucidate the process of synaptic plasticity. We therefore employed optical methods including FRET, FLIM, photoactivatable proteins and caged compounds to elucidate the mechanism of synaptic plasticity, with an emphasis on structural modification of dendritic spine seen during long-term potentiation (LTP) of hippocampal CA1 pyramidal neurons.

After the induction of LTP, the remodeling of actin cytoskeleton and its polymerization is the first thing to happen. Active cofilin is massively transported to the spine and severs the F-actin, which likely generates new free ends of actin from where new filament starts growing. Thereafter, these two proteins forms a stable complex at the base of spine head thereby forming a stable F-actin and regulating spine expansion.
In contrast, the postsynaptic density (PSD) was independently remodeled, as PSD scaffolding proteins did not change their amount and localization until late protein synthesis-dependent third phase. Our findings show how and when spine substructures are remodeled during LTP and explain why synaptic plasticity rules change over time.

Selected publications

PubMed  Hayashi Y

1 Wang DO, Matsuno H, Ikeda S, Nakamura A, Yanagisawa H, Hayashi Y, and Okamoto A: "A quick and simple FISH protocol with hybridization-sensitive fluorescent linear oligodeoxynucleotide probes.", RNA (2012)

2 Mower AF, Kwok S, Yu H, Majewska AK, Okamoto KI, Hayashi Y, and Sur M: "Experience-dependent regulation of CaMKII activity within single visual cortex synapses in vivo.", Proc Natl Acad Sci U S A (2011)

3 Hayashi MK, Tang C, Verpelli C, Narayanan R, Stearns MH, Xu RM, Li H, Sala C, and Hayashi Y: "The postsynaptic density proteins Homer and Shank form a polymeric network structure.", Cell, 137(1), 159-71 (2009)

4 Kim MJ, Futai K, Jo J, Hayashi Y, Cho K, and Sheng M: "Synaptic accumulation of PSD-95 and synaptic function regulated by phosphorylation of serine-295 of PSD-95.", Neuron, 56(3), 488-502 (2007)

5 Okamoto K, Narayanan R, Lee SH, Murata K, and Hayashi Y: "The role of CaMKII as an F-actin-bundling protein crucial for maintenance of dendritic spine structure.", Proc Natl Acad Sci U S A, 104(15), 6418-23 (2007)

6 Futai K, Kim MJ, Hashikawa T, Scheiffele P, Sheng M, and Hayashi Y: "Retrograde modulation of presynaptic release probability through signaling mediated by PSD-95-neuroligin.", Nat Neurosci, 10(2), 186-95 (2007)




Yasunori Hayashi M.D., Ph.D.
Brain Science Institute, RIKEN
 Hirosawa, Wako, Saitama, 351-0198 Japan

"The goal of my laboratory is to elucidate the molecular mechanism of learning and memory"

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